Bioactive spiropyrrolizidine oxindole alkaloid enantiomers from Isatis indigotica Fortune. Issue 48 (4th December 2018)

• Record Type: Journal Article
• Authors: Liu, Si-Fan; Lin, Bin; Xi, Yu-Fei; Zhou, Le; Lou, Li-Li; Huang, Xiao-Xiao; Wang, Xiao-Bo; Song, Shao-Jiang
• Is Part Of: Organic & biomolecular chemistry. Volume 16:Issue 48(2018)
• Page Start: 9430
• Page End: 9439
• Publication Date: 2018-12-04
• Subjects: Chemistry, Organic -- Periodicals; Bioorganic chemistry -- Periodicals; Chemistry, Physical organic -- Periodicals; 547
• DOI: 10.1039/c8ob02046a
• Languages: English
• ISSNs: 1477-0520

Abstract

Abstract : Four pairs of new alkaloids, isatindigotindoline A–D, were isolated from Isatis indigotica, and were evaluated for their anti-Aβ1–42 aggregation effects. Abstract : Four pairs of new spiropyrrolizidine oxindole enantiomers (1a/1b–4a/4b ) were isolated from the leaves of Isatis indigotica Fortune. Their structures and absolute configurations were elucidated by a combination of NMR spectroscopic analyses, experimental and calculated electronic circular dichroism (ECD) and the assistance of quantum chemical predictions (QCP) of 13 C NMR chemical shifts. Notably, all the isolated spiropyrrolizidine oxindoles are reported as natural products for the first time. The biosynthetic pathway of these unique structures was proposed to be formed by cycloaddition reaction. In addition, all the compounds were evaluated for their inhibitory effects on β-amyloid aggregation by ThT assay, and the optically pure compounds1a /1b and2a /2b exhibited better Aβ1–42 aggregation inhibition potency (85.8% and 73.6%, 71.5% and 75.8%, respectively) at a concentration of 20 μM, compared with the positive control curcumin (57.0%). The difference of the inhibitory pattern caused by chirality was also explained by molecular docking studies.